Idiopathic young-onset Fahr’s disease with schizophrenia-like presentation: a case report

This case report describes an exceptionally rare case in which a prior diagnosis of schizophrenia was later determined to be early-onset Fahr’s disease, linked to a genetic mutation in the SLC20A2 gene. Initially, the patient exhibited symptoms resembling schizophrenia, including aggression and hostility, and was highly susceptible to medication side effects such as restlessness and Parkinsonism. Despite maintaining independent activities of daily living, his neurological examinations revealed hidden weakness on the left side. Following adjustments to the medication regimen, stability was achieved with residual psychotic symptoms under treatment with Risperidone 1.5mg/day, Valproic acid 1500mg/day, and Quetiapine 37.5mg/day. This case underscores the importance of conducting comprehensive imaging studies at the time of initial psychiatric diagnosis, regardless of the apparent typicality of the presentation. Additionally, it emphasizes the need for patience and adherence to the “Start Low and Go Slow” approach in medication management to minimize the risk of exacerbating psychiatric symptoms and aggression.


Introduction
Fahr's disease is a rare neurodegenerative disorder with a prevalence of <1/1,000,000 and commonly affects people aged 40s and 50s.Fahr's disease is characterized by idiopathic calcification of the bilateral basal ganglia and striopallidodentate area.The clinical presentation of this disease varies and may include psychosis, cognitive impairment, seizures, headaches, and motor function deterioration (1).The optimal treatment for Fahr's disease remains unclear (2).While antipsychotics can offer symptomatic management of psychosis, patients with Fahr's disease are more susceptible to side effects such as extrapyramidal syndromes (3).Achieving a balance between treatment and medicationrelated adverse effects is crucial in helping patients control symptoms and preserve their functioning.In this report, we present a case of early-onset Fahr's disease that initially with symptoms resembling schizophrenia and further discuss the treatment experience and response.The case report has been approved by the Institutional Review Board, National Cheng Kung University Hospital (B-EC-113-002)

Case
The 20-year-old unmarried male, diagnosed with schizophrenia at 17, was hospitalized due to psychotic manifestations, characterized by auditory hallucinations, persecutory delusions, disorganized thoughts, and violent behaviors with no history of mental, genetic, or neurological disorders.Additionally, the patient had neither family history of similar complaints nor documented history of Parkinsonism, infectious etiologies, or substance abuse at the time of initial diagnosis.The patient maintained modest academic performance during the period spanning from 17 to 19 years while experiencing mild auditory hallucination and paranoid ideation, managed with a regimen of Paliperidone at a dosage of 3mg per day.However, a relapse of psychotic symptoms occurred following the discontinuation of medication without medical consultation, prompting the subsequent adjustments in treatment modalities.Initially, Paliperidone at 3mg daily for one month yielded a suboptimal response, leading to the transition to a combination regimen comprising Aripiprazole at 10mg daily alongside Biperiden at 2mg daily, commenced two months preceding the current admission.Moreover, Fluoxetine at 10mg daily was introduced 1.5 months before the admission, because of compulsive hand washing.Further alterations in pharmacotherapy included the incorporation of Risperidone oral solution at 1mg daily for one month, in conjunction with Flupentixol Decanoate at 20mg administered once biweekly.Upon admission, the patient was receiving Aripiprazole at 10mg daily, Fluoxetine at 10mg daily, Risperidone at 2mg daily, Flupentixol Decanoate at 20mg biweekly, and Biperiden at 2mg daily.Despite the multifaceted pharmacological approach, symptomatic relief remained elusive, with concurrent escalation of aggressive behaviors.
Throughout his hospitalization, the patient exhibited concealed left-side weakness and mild muscle rigidity.He maintained a stable gait and independent activities of daily living.Neurological examinations and physical examinations showed negative findings except for the aforementioned.Brain computed tomography (CT) and magnetic resonance imaging (MRI) showed calcifications in the bilateral globus pallidus, caudate nucleus, thalami, and subcortical areas, with no evident vessel abnormalities (Figure 1).Notably, the patient displayed marked aggression and hostility and exhibited pronounced susceptibility to medication-related adverse effects, such as restlessness and Parkinsonism.To optimize therapeutic efficacy while mitigating risks, the medication regimen was transitioned from Aripiprazole (5-10mg/day) to Olanzapine  From the patient's perspective, as assessed through the Health, Personality, and Habit Test -A Form Scale, he continued to harbor beliefs that he was being followed, spied on, and subjected to potential harm or attack.He perceived a sense of loss of autonomy, with the conviction that others had control over his body and were privy to his thoughts.Despite recognizing the severity and progressive nature of his mental disorder, he expressed feelings of frustration and sadness regarding his experiences.Acknowledging the necessity for long-term treatment, the patient consented to transfer to a psychiatric chronic ward to facilitate disease management and rehabilitation.

Discussion
Fahr's disease is a neurodegenerative disorder that can occur as a secondary manifestation of hereditary or endocrine diseases.The most common site of abnormal calcium deposits is the globus pallidus.Additionally, deposits have been observed in the globus pallidus dentate nuclei, thalami, and other deep cortical structures (2,(4)(5)(6).Fahr's disease can manifest at any age, but the most frequent onset age is between the 30s and 50s (2,6,7).The main clinical presentations include neurological symptoms such as seizures, Parkinsonism, rigidity, ataxia, dysarthria, tremor, and headaches, as well as psychiatric symptoms such as mood disorders, psychotic symptoms, irritability, aggressiveness, lack of impulse control, regressive behaviors, behavioral disinhibition, obsessive-compulsive spectrum symptoms, and cognitive and psychomotor impairment.Extrapyramidal symptoms are observed in 50-56% of initial presentations, while psychiatric symptoms such as psychosis, mania, anxiety, and apathy contribute to 40% (3,(7)(8)(9).Two clinical variants of Fahr's disease were proposed by other studies: early onset and late onset (10).In the early onset variant, psychiatric symptoms were found to present earlier to movement abnormalities.While the late-onset variant tends to be an initial presentation with severe movement disorder followed by dementia-like symptoms.The present case echoed this finding from the literature.He had no neurological signs and movement abnormalities in the background of florid psychosis.Moreover, instead of muscle rigidity, he was more susceptible to akathisia mimicked as worsening psychotic symptoms and aggression.
The physical and occupational therapy programs, such as passive and active physiotherapy, muscle strengthening exercises, and independence training, integrated according to patients' specific motor deficits may improve their mobility, preserve their functional independence, and enhance their quality of life (22).
In summary, Fahr's disease is a neurodegenerative disorder presenting with various neuropsychiatric symptoms that are often underestimated.This case highlights two important concepts regarding the early onset of psychotic symptoms: (1) comprehensive differential diagnosis, emphasizing the need for thorough clinical assessment and meticulous consideration of various potential diagnoses, particularly when the patient has atypical presentation and unexpected response to therapy; and (2) individual variation in sensitivity to medication, suggesting the importance of initiating treatment with a low dose and gradually titrating it to achieve the optimal dosage through careful titration.

FIGURE 1
FIGURE 1 Basal ganglia calcification in the brain computed tomography: (A) coronal plane; (B) sagittal plane; (C) transverse plane.Basal ganglia calcification in the brain magnetic resonance imaging: (D) sagittal plane.
7.5mg/day; administered for a total of 18 days), and ultimately to Risperidone (1mg/day).The patient's blood investigations including ceruloplasmin, vitamin D, calcium, magnesium, phosphate, thyroid and parathyroid hormone, and alkaline phosphatase showed no abnormalities.Therefore, given the poor response to the patient's psychotic and aggressive behaviors, and high susceptibility to psychotropic adverse effects, with supportive brain CT and MRI findings, a diagnosis of Fahr's disease was considered.The revised diagnosis was further confirmed by genetic testing unveiling a deficit in the SLC20SA gene.Following four weeks of treatment adjustment, the patient was stabilized on a regimen comprising Risperidone 1.5mg/day, Valproic acid 1500mg/ day, and Quetiapine 37.5mg/day.Upon discharge from the psychiatric acute ward, the patient had mild psychotic symptoms devoid of disruptive behaviors or violence. (